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竞争性内源性 RNA 网络的构建和分析揭示了长非编码 RNA 在肝纤维化中的调控作用。

Reconstruction and analysis of competitive endogenous RNA network reveals regulatory role of long non‑coding RNAs in hepatic fibrosis.

机构信息

Experimental Center of Clinical Research, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui 230031, P.R. China.

Department of Pharmacy, Anhui Provincial Hospital, Hefei, Anhui 230001, P.R. China.

出版信息

Mol Med Rep. 2019 Nov;20(5):4091-4100. doi: 10.3892/mmr.2019.10682. Epub 2019 Sep 13.

Abstract

Hepatic fibrosis (HF), one of the leading global health problems, is defined as aberrant and excess production of extracellular matrix components. The pathogenesis of HF is complex and poorly understood. Long non‑coding RNAs (LncRNAs) can interact with microRNAs (miRNAs) as competing endogenous RNAs (ceRNAs) to regulate the expression of target genes, which play a significant role in the initiation and progression of HF. In the present study, the LncRNA‑associated ceRNA network was reconstructed based on LncRNA, miRNA and mRNA expression profiles that were downloaded from National Center for Biotechnology Information Gene Expression Omnibus. Bioinformatics assessments including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed with Database for Annotation, Visualization and Integration Discovery. The ceRNA network was composed of 220 LncRNA nodes, 24 miRNA nodes, 164 mRNA nodes and 1,149 edges. Functional assays identified that a total of 338 GO terms and 25 pathways, including regulation of cytokine and collagen, and the transforming growth factor‑β and Toll‑like receptor signaling pathways, were significantly enriched. In addition, 4 LncRNAs (NONMMUT036242, XR_877072, XR_378619 and XR_378418) were highly related to HF and thereby chosen as key LncRNAs. The present study uncovered a ceRNA network that could further the understanding of the mechanisms underlying HF development and provide potential novel markers for clinical diagnosis and targets for treatment.

摘要

肝纤维化(HF)是全球主要健康问题之一,定义为细胞外基质成分的异常和过度产生。HF 的发病机制复杂且尚未完全阐明。长链非编码 RNA(lncRNA)可以作为竞争性内源 RNA(ceRNA)与 microRNA(miRNA)相互作用来调节靶基因的表达,在 HF 的发生和进展中发挥重要作用。本研究基于从美国国立生物技术信息中心基因表达综合数据库下载的 lncRNA、miRNA 和 mRNA 表达谱,重建了 lncRNA 相关 ceRNA 网络。通过数据库注释、可视化和综合发现(Database for Annotation, Visualization and Integration Discovery)进行了基因本体论(GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes)通路分析等生物信息学评估。ceRNA 网络由 220 个 lncRNA 节点、24 个 miRNA 节点、164 个 mRNA 节点和 1149 个边组成。功能分析确定了总共 338 个 GO 术语和 25 条通路,包括细胞因子和胶原蛋白的调节以及转化生长因子-β和 Toll 样受体信号通路,这些通路均显著富集。此外,4 个 lncRNA(NONMMUT036242、XR_877072、XR_378619 和 XR_378418)与 HF 高度相关,因此被选为关键 lncRNA。本研究揭示了一个 ceRNA 网络,可进一步了解 HF 发生发展的机制,并为临床诊断提供潜在的新标志物和治疗靶点。

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